Intractable pain is chronic pain for which there is little or no effective therapy. The long term objective of this work is to create a therapeutic agent that will chemically ablate peripheral pain nerves involved in intractable pain and thereby treat painful human disorders in which the pain does not serve a useful purpose. The specific aims of this phase l proposal are to further develop a drug conjugate which has been shown to be cytotoxic for pain receptor-bearing cells, using in vitro and in vivo assays. When administered to humans, the drug conjugate will be injected locally into the area of pain, and become internalized in and kill the pain nerve, while sparing other types of sensory, somatic motor and autonomic nerves. There are a variety of neurological, orthopedic, rheumatological, and oncological pain disorders for which this drug will have application. This is the first time that a selective drug therapy has been devised to specifically ablate pain nerves as a means of treating intractable pain. It will provide an advantage in its specificity for ablating pain nerves over present neurosurgical methods and will have the advantage over present drug therapies in that this drug will be nonaddictive.